[!INFO] Definitions:
left ventricular hypertrophy = increased left ventricular mass.
Hypertrophy is divided into concentric and eccentric based on the "relative ventricular wall thickness".
This in turn is defined as "ventricular wall thickness divided by LV diastolic diameter".

• If relative wall thickness is high, it's called concentric.
• If relative wall thickness is low, it's called eccentric. Source

Congenital infections

Source

Vertical transmission can occur from other to baby by

• Transplacental
• Via Ascending infection
• Intrapartum - in birth canal
• Post partum
  • Via breast milk
  • Via contact

A) Infections acquired transplacentally:

[!INFO] Mnemonic CLAP TORCHES

1. CLAP - Chickekpox, Listerial, AIDS, Parvovirus b19
2. ToRCHES - Toxoplasmosis, Rubella, CMV, Herpes, Enterovirus, Syphilis
3. Also Zika virus

B) Infections acquired from birth canal

[!INFO] Mnemonic: 3 viruses, 5 bacteria

• HSV, HIV, Hep B, GEL-CG (or LG-ECG)
  • GEL-CG = Group B Strep (Agalactiae), E coli, Listeria, Gonococcus, Chlamydia

[!INFO] Viruses which only rarely cross the placenta
HIV, HSV, Hep B, EBV.
More frequently, they are transmitted perinetally

Decription of transplacental infections

#TODO read routes of infection from this source.

Congenital varicella infection

Presentation depends on time of infection:

1. mother is infected before POA of 20 -> neonatal varicella syndrome
   1. Scars - cicatrix, Limb hypoplasia, cataracts, chorioretinitis , microcephalus, seizures
   2. prevent with VZIG (give empirically if mother's varicella antibody status cannot be determined within 96 hours) Source
2. Mother develops vessicles -5 to +2 days after delivery:
   1. 
   2. (because the foetus doesn't have time to acquire protective maternal antibodies)
   3. Severe foetal varicella infection
   4. Give VZIG to mother and VZIG to baby upon delivery (or as soon as mother develops vesicles)

[!INFO] mnemonic: patient numbers
Phase I - double digits
Phase II - Triple digits
Phase III - quadruple digits, also C being the 3rd letter of the alphabet, phase III trials 'compare' efficacy -> RCTs.

[!INFO] The Big 5 STIs
Chlamydia, gonorrhoea, Syphilis, HIV, hepatitis B,
and trichomoniasis.

Rabies post exposure prophylaxis

[[AntirabiesPostExposure.pdf]]
2 site intradermal - 2,2,2,0,2
on day 0,3,7,30

• The standard treatment in government hospitals.

4 site intradermal is similar - 4,2,2,0,2
recommended for late presentaion, border line exposure or major exposure from observable healthy domestic animal.

IM arv course is on day 0,3,7,14,30.
something called the 2-2-1 regimen is used for minor exposurse.

Macrophage activation syndrome (MAS)⭐

• Acutely ill patient; including CNS dysfunction
• Non-remitting high fever.
• Diagnosis: demonstration of haemophagocytosis in bone marrow samples.
• Management: High dose IV corticosteroids or High dose IVIG +/- cylcosporine / cyclophosphamide.

Caused by HHV-4. (human herpevirus 4) [[viralClassificationFamilies.png]]

⭐MCD in adults:
- NSAID induced
- NSAIDS can cause haemodynamically mediated AKI and Acute Interstitial nephritis - which can lead to MCD.Source
- Lithium, mercury - (both also a cause for membranous nephropathy)
- Malignancies, particulartly haematologic ones: Hodgkin lymphoma and non hodgkin lymphoma (paraneoplastic)

• Infections like syphilis, TB, mycoplasma.

FSGS (Focal segmental glomerulosclerosis)

- ![SelectiveVsNonSelectiveProteinLossInGlomerulonephritis.png](SelectiveVsNonSelectiveProteinLossInGlomerulonephritis.png)
- Electrophoresis of urine samples in different diseases: [Source](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874928/)
- Despite this electrophoresis clearly showing that MCD doesn't loose much IgG, *infection is a well known complication of minimal change disease*. [Source](https://emedicine.medscape.com/article/244631-overview#showall)(maybe due to complement loss, steroids etc)

Membranous glomerulonephritis

⭐Membranous nephropathy -
- Need to exclude hepatitis B, SLE, thyroiditis, some drugs (penicillamine, gold / mercury, captopril) and malignancy.
- Associated malignancies: prostate, lung, lymphoma, leukemia
Prognosis - rule of thirds (passMedicine)

• one-third: spontaneous remission
• one-third: remain proteinuric
• one-third: develop ESRF

⭐Charcot Marie Tooth disease

[!TIP] Mnemonic:
Marie : Odd ones out (odd numbers affect the 'external' myelin

• It is the commonest inherited neuropathy
• CMT-1: "Demyelinating" Pain and temperature are usually not affected because they are carried by unmyelinated "C-Fibers". Type 1 is #autosomalDominant inherited.
• CMT-2: "Axonal" Typically #autosomalDominant
• CMT-4: #autosomal-Recessive

[!INFO] see also
[[General Medicine 4#Q 12 Rabies prophylaxis|Rabies prophylaxis]]

Eosinophillic, **cytoplasmic** inclusions of viral proteins visible in the *hippocampus and cerebellum*. 

• Viruses multiply in the muscle, enter neurons and then travel in a retrograde direction towards the CNS in motor and sensory nerves.(can cause numbness around the wound)
• Hence why IG is given to muscle around the bite site.
  (because retrograde migration of the birus takes time -> in head bites, the inoculation is closer to the brain)
• Majority is encephalitic (furious) rabies.
  • The classic presentation of encephalitic rabies includes fever, hydrophobia, pharyngeal spasms, and hyperactivity subsiding to paralysis, coma and death.
• 20% of patients present with paralytic rabies (aka Dumb rabies):
  • Fewer than 20 percent of rabies patients present with an ascending paralysis, which can mimic Guillain-Barré syndrome

• Immunosuppresed people get complications -> pyrimethamine is first line drug.

PKD genes encode the polycystin proteins. Mutations of these cause decreased intracellular calcium in the principal cells of the collecting duct -> dysoriented cell division -> cyst formation.
Polycystin 1 (in PKD1) is a regulator of tubular epithelial cell adhesion and differentiation. Polycystin 2 (in PKD2) is an ion channel. These are required for function of cilia of the tubular epithelium which are in turn required for flow sensing. Impaired flow sensing causes a defect in proliferation and differentiation -> cysts.
Cyst formation occurs only in 5-10% of nephrons but that's enough to cause renomegaly.

• ⭐Male gender
• ⭐High urinary sodium excretion
• ⭐hypertension - patients with larger kidneys tend to have hypertension.
  Seronegative RA - affects wrists more than fingers and has less symmetrical involvement.

• The triad of rheumatoid arthritis, splenomegaly, and neutropenia.

Caplan Syndrome

• Rheumatoid arthritis with Intralpumonary nodules.
• Seen in patients with pneumoconioses.
• 
• Eye:
  • No uveitis.
    Rheumatoid effusion
• Can be exudative effusions
  • associated with rheumatoid nodules on the pleural surface.
  • Findings:
    • Characteristically low ph (<7.3) and low glucose (<60mg/dL)
    • white cell count <5000/mm3
    • high LDH
    • Multinucleated macrophages
• Cholesterol effusion (chyliform effusions)
• Empyema and pyopneumothorax
• Pneumothorax or haemopneumothorax - necrosis of pleural nodules can cause a bronchopleural fistula or haemopneumothorax.

Hookworm

• Necator americanus ("American murderer") , ancylostoma duodenale

• and ancylostoma ceylonicum

• Ancylostoma ceylonicum is endemic in dogs and cats as well as humans.

• Ancylostoma caninum from dogs can infect human intestine but does not reach reproductive maturity.

• Another group of hookworms infecting animals can penetrate the human skin causing cutaneous larva migrans (A. braziliense, A. caninum, Uncinaria stenocephala). Other than A. caninum noted above, these parasites do not develop further after their larvae penetrate human skin

[!TIP] Mnemonic:
Hookworm - larva migrans.(slow)
Strongyloides -> larva currens (fast)
Strongyloides are strong -> therefore move fast -> "currens"

Proteins which are normally soluble start getting deposited extracellularly as beta pleted fibrils.
1. Dialysis-related amyloidosis (DRA) is a disabling disease characterized by accumulation and tissue deposition of amyloid fibrils consisting of beta2-microglobulin (beta2-m) (Aβ2M) in the bone, periarticular structures, and viscera of patients with end-stage kidney disease. Beta2-m is a component of the major histocompatibility complex that is present on cell surfaces and is normally cleared by glomerular filtration
2. Aβ2M amyloidosis presents with carpal tunnel syndrome.

[!INFO] Once the presense of amyloid is found

the precursor protein must be determined.
(Both (AL and AA) have the beta pleted sheet structure) (Harrison's - page 804)
| Type | Constituent |
| ------------------------- | --------------------------------------------------------------------------------------------------------------------------------- |
| AL Amyloidosis | Deposition of Ig Light chain fragments |
| Transthyretin amyloidosis | |
Commonest involved organs:

1. Kidney
2. heart

The symptoms and signs of AL and AA cannot reliably be distinguished. - Harrison's

AA amyloido is derived from a serum precursor called serum amyloid associated protein. (SAA protein).
It is made in the liver under the stimulation of IL-1, and IL-6.

A-beta amyloid (Aβ amyloid)

Found in Alzheimer's disease.
The precursor for this is Amyloid precursor proteins. (APP)

- *Probenecid* - avoid in renal impairment
- **Anakinra** - *IL-1 inhibitor*; very expensive.

• Persistent inflammation.
• Skin and periarticular urate crystal deposits (tophi) causing chronic pain and overlying skin ulceration.
• Punched out bone cysts on X ray.
• Urate nephropathy with renal impairment.
  Treatment:
• It's associated with chronic diuretic use -> stop or change diuretics.
  #2015MCQ/Q33

[!WARNING]
Hypoparathyroidism in the image is probably incorrect; most sources say hyperparathyroidism.

P is for positive - peudogout pyrophosphate crystals show positive birefrigence.

- (?not following viral infection)
- Also plantar fasciits, achilles tendinits, balanitis, anterior uveitis

• Enthesitis causing plantar fascitis or achilles tendon enthesitis can occur. Also dacytilitis

• Skin and nail lesions resembling psoriasis

  • DMARDS and biologics are usually used when arthritis becomes "chronic refractory." - UpToDate

• Reiters is more prevalent among indiviuals with HIV. It can predate the symptoms of HIV. Can present as oligoarthritis.

• Listeria is a beta haemolytic gram +ve bacillus.

• They are ubiquitous in the environment and can be present in the human gut.

• Spread via contaminated food.

  • Salads, cold meat, cheeses, unpasteurized milk
  • Mnemonic: (The chilled section of the buffet)
  • They can even survive and reproduce at refrigerator temperatures.

• Diagnosis requires blood culture; Faecal culture is not sensitive.

• Suspect due to clinical context as infections can occur in clusters / outbreaks.

• They can cause a watery diarrhoea [[2022-November#^5eaea3|watery Diarrhoea]]

• Clinical manifestations:

  • Either gastroenteritis or invasive disease
  • Invasive disease occurs in pregnant women, people over 65 or neonates. (incubation period is 2 weeks)
    • Invasive disease in non pregnant people can cause meningitis. (some will not have classical features of meningitis)
    • invasive disease in pregnant women usually doesn't cause meningitis.
  • febrile gastroenteritis. (incubation period is 1 day)

• In immunocompetent people, infection is asymptomatic.

• The bacteria multiply intracellularly and therefore, require cell mediated immunity for control.

  • i.e can't be cultured on routine media. (?do they require cellular media)

• Therefore, following groups are at risk;

  • Elderly
  • Neonates
  • Pregnant women - Mother usually has mild illness; Choriamnionitis -> transplancental spread -> spotaneous abortion, early infant death are the risks.
  • Immunocompromised patients

• In at risk patients, bacteraemia leads to high fever without localizing signs leading to endocarditis, peritonitis, osteomyelitis, septic arthritis, cholecystitis and pneumonia, meningitis and occuloglandular listeriosis (ophthalmitis and lymph node enlargement - Parinaud syndrome).

• Treatment: Ceftriaxones are ineffective. Ampicillin + gentamicin (as this combination shows synergy) for at least 2 weeks.

  • Longer for CNS infection and compromised patients.

^36d6c8

[!TIP] Mnemonic: TAMPAX -> "TAMPOX"

TAMponade - Pulsus paradoxus and only X descent are seen. (Y descent is absent)
Constrictive -> "Konsrictive" -> Kussmaul sign [[#^36d6c8]] is present in constrictive pericarditis.
| Left and Right ventricular diastolic pressure and left and right atrial pressures (PCWP) all rise to match the pericardial pressure. (i.e ?no pressure gradient from atrium to ventricle -> impaired flow across TV -> absent Y descent) | ?Greatly increased ventricular interdependance |

• Acute toxicity can produce motor symptoms -> Course tremmor.
  

• Patient it always > 50 years old; sudden onset pain and stiffness (but NOT WEAKNESS) of limb girdles / proximal muscles, associated with raised inflammatory markers.
• But inflammatory markers are raised (⬆ ESR and CRP)
  #2015MCQ/Q36

Always over 50;

• GCA is classified as large vessel vasculitis but also involves medium and small arteries.
  • One of which is the temporal artery.
  • Other arteries: ophthalmic, occipital, vertebral, posterior ciliary
  • 
• Inflammatory, granulomatous, arteritis or large cerebral arteries.
• Histology: Transmural inflammation (all 3 layers) of arteries, with Cellular infiltrates of CD4+ cells, macrophages and giant cells.
  • Can also cause mononeuritis mulitplex. Source
  • 
  • Elevated ESR is a hallmark of GCA.
  • However, ESR can be normal in upto 20%; Therefore, ⬆ESR doesn't exclude GCA.
• Definitive Dx : temporal artery biopsy. Patchy lesions -> >1cm needs to be examined.
  • temporal artery biopsy as a specificity of 100% but sensitivity of 15 to 87% (i.e negative biopsy doesn't exclude disease)
  • Halo sign on colour doppler is suggestive of the disease.
  • ALP and AST can be elevated.
• It's a self limiting condition.
• Steroids can reduce abdominal pain, NSAIDS for joint pain +/- steroid sparing azathioprine and cylcophosphamide.
• Evidence for use of steroid is inconsistent. - passMedicine

[!INFO] The only enterovirus we have a vaccine for is polio virus.